Isolation and synthesis of bioactive molecules against Schistosoma mansoni from Boscia senegalensis (Pers) Lam. ex Poir. (Capparaceae) bark extracts used in West African traditional medicine

• Boscia senegalensis shows anti-schistosomal potential but is underexplored. • Bioassay-guided stem bark fractionation yielded a novel hexalobine derivative • Crystalline sponge technology enabled structure elucidation of trace isolates • Hexalobine derivatives were successfully synthesized for anti-schistosomal evaluation • Compound 3 showed potent in vitro activity and highest in vivo worm reduction Boscia senegalensis (Pers.) plant parts are widely utilized in West African traditional medicine for various ailments, including schistosomiasis. Despite its extensive use, its potential for discovering novel bioactive compounds has not been fully harnessed. To explore natural product alternatives to praziquantel for treating schistosomiasis, we investigated B. senegalensis bark extracts for new bioactive compounds against Schistosoma mansoni . Bioassay-guided fractionation of the active non-polar fractions led to the isolation of known 3,6-hexalobine A ( 1 ) and a novel hexalobine derivative, 6-(3-methylbut-2-en-1-yl)-3-((2-methyltetrahydro-2 H -pyran-2-yl)methyl)-1 H -indole ( 2 ), identified using the crystalline sponge technology. Compounds 1 and 2 , along with two other hexalobine derivatives ( 3 and 4), were synthesized and evaluated for anti-schistosomal activity. The compounds exhibited dose-dependent in vitro anti-schistosomal effects against both newly transformed schistosomula (NTS) and adult worms. Notably, compound 3 demonstrated the highest activity against the adult worms with an IC 50 of 0.16 μM. In in vivo experiments, 3 showed varying total worm burden reduction with different doses, achieving the maximum reduction of 71.4%. These findings underscore the potential of 3 for further investigation in anti-schistosomal drug discovery and development.